Serum free igf-i during a hyperinsulinemic clamp following three days administration of igf-i versus saline. Frystyk, J., M. Hussain, C. Skjrbk, O. Schmitz, J. S. Christiansen, E. R. Froesch, and H. Rskov. Institute of Experimental Clinical Research, Medical Research Laboratories and Medical Department M, Aarhus University Hospital, Aarhus, Denmark, Department of Internal Medicine, Division of Endocrinology and Metabolism, Zurich University Hospital, Zurich, Switzerland.
APStracts 4:0111E, 1997.
In a randomized crossover study in 8 healthy subjects we compared the effect of three days of continuous subcutaneous administration of IGF-I (10 [mu]g/kg/h) and saline on fasting serum levels of free insulin-like growth factor-I (IGF-I), total (extractable) IGF-I and IGF-binding protein-1 (IGFBP-1) and IGFBP-3. On the third day a hyperinsulinemic euglycemic and hypoglycemic clamp was performed. When comparing preclamp (baseline) levels after three days, IGF-I administration had increased total IGF-I from 225 +/- 21 (mean +/- SEM) to 1003 +/- 46 [mu]g/l (p < 0.0001), free IGF-I from 0.5 +/- 0.2 to 10.4 +/- 1.7 [mu]g/l (p < 0.001), IGFBP-3 from 2908 +/- 148 to 3591 +/- 179 [mu]g/l (p < 0.01) and IGFBP-1 from 7.6 +/- 3.8 to 19.6 +/- 2.5 [mu]g/l (p < 0.01). During the clamp levels of free IGF-I increased gradually from baseline to 1.0 +/- 0.3 [mu]g/l (saline; p < 0.01) and to 19.6 +/- 4.7 [mu]g/l (IGF-I; p < 0.005). Concomitantly, levels of IGFBP-1 decreased gradually from baseline to 4.1 +/- 2.3 [mu]g/l (saline; p < 0.0005) and to 4.6 +/- 1.8 [mu]g/l (IGF-I; p < 0.0001). Total IGF-I exhibited minor changes only during the clamp (p < 0.05), and IGFBP-3 was unchanged. In conclusion, administration of IGF-I increased total IGF-I about 4-fold, whereas free IGF-I increased about 20-fold. Noteworthy, in both situations a further 2-fold increase in free IGF -I was observed during the hyperinsulinemic clamp, concomitantly with a decrease in IGFBP-1. This supports the hypothesis that IGFBP-1 is important in the short-term regulation of free IGF-I in vivo.

Received 14 January 1997; accepted in final form 30 April 1997.
APS Manuscript Number E21-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 11 June 1997